APPLICANT'S ABSTRACT: This is a proposal for an Independent Scientist Award (KO2) to expand the applicant's research program on alcohol-associated neuropsychological impairment and treatment-outcome. The aim is to develop a multilevel neuroscience approach for studying these complex brain-behavior relations by pursuing specialized collaboration and advanced training in quantitative and neuroimaging methodologies. The first career objective is to develop further expertise in complex variable-centered and person-centered quantitative methods, as well as methods for integrating these two analytic approaches. Specialized quantitative skills will be developed through collaboration with experts and participation in advanced training institutes. These skills will be used to test complex mediation and moderation models of the effects of alcohol-related neuropsychological impairment on treatment outcomes in three existing NIAAA and private data bases. The second career objective is to gain expertise in magnetic resonance imaging (MRI) and functional MRI (fMRI) methods. Career development in neuroimaging will comprise formal course work, hands-on training, and collaboration with experts. Neuroimaging training will be applied to a preliminary study of the influence of family histories of alcoholism and depression on neuropsychological impairment and neuroanatomical changes in youth with psychiatric diagnoses compared to a control group with no psychiatric diagnoses. Hypotheses of heightened neurocognitive vulnerability and symptom severity in high-risk FH+ youth will be tested.